#76 Hep SA Community News

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#76 • January 2018

Community News

Hepatitis D Special

Hepatitis D: An Introduction There are five known hepatitis viruses, helpfully named A, B, C, D and E. The hepatitis D virus, HDV (sometimes known as hepatitis delta), is relatively little-known, because it can only live alongside hepatitis B. This means it needs to be acquired at the same time as hepatitis B, or else someone already living with hepatitis B can be infected with it later on. Because of this HDV is known as a satellite virus. It is estimated that, worldwide, approximately 5% of people living with hepatitis B also have hepatitis D. The hepatitis D virus is transmitted by infected blood

and body fluids. This can happen from direct exposure to blood, through sharing unsterile injecting drug or body piercing equipment, and through unprotected sex. You can protect yourself from both HBV and HDV by: • vaccinating against hepatitis B • practicing safe sex (using a condom) • not sharing injecting equipment, including tourniquets, spoons and filters (use new and sterile injecting equipment for each injection) • avoiding tattooing, piercing, dental and January 2017 •

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cosmetic procedures where equipment is not sterilised • ensuring all equipment is sterilised and no blood to bloodstream contact occurs when undergoing cultural rituals where blood is involved • following the Blood Rule in sport • not sharing toothbrushes, razors, needles, syringes, personal hygiene items

Continued inside…

FREE!

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Introduction Hepatitis SA provides free information and education on viral hepatitis, and support to people living with viral hepatitis.

Welcome to a special edition of the Hepatitis SA Community News, published between two of our normally scheduled issues. Here we take a look at hepatitis D, the little-known but potentially devastating virus that can infect people alongside hepatitis B. Our next regular issue will be published in March.

Street Address: 3 Hackney Road, Hackney

Cover: Image of a hepatitis D virus ribozyme complex, courtesy of the Science Photo Library

Postal Address:

Correspondence: Please send all correspondence to The Editor at PO Box 782, Kent Town, SA 5071, or email editor@hepatitissa.asn.au.

Phone:

Editor: James Morrison

PO Box 782 Kent Town SA 5071

Fax:

(08) 8362 8443 1800 437 222 (08) 8362 8559

Online:

www.hepsa.asn.au admin@hepatitissa.asn.au

Do you have a hepatitis D story? Do you have experience living with hepatitis D? Are you interested in sharing your story with our readers? Please get in touch with us at editor@hepsa.asn.au or on 8362 8443. Anonymity can be guaranteed.

HEPATITIS SA BOARD Chair Arieta Papadelos

Contents

Vice Chair Bill Gaston

Secretary Lindsay Krassnitzer

1 Hepatitis D: An Introduction

Treasurer Sam Raven Ordinary Members Catherine Ferguson Ratan Gazmere Kirsten Hicks Sharon Jennings Maggie McCabe Kerry Paterson (EO) Deborah Perks

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4 Hepatitis D Treatment 6 Hepatitis D: Personal Stories 8 Further Reading Disclaimer: Views expressed in this newsletter are not necessarily those of Hepatitis SA. Information contained in this newsletter is not intended to take the place of medical advice given by your doctor or specialist. We welcome contributions from Hepatitis SA members and the general public. SA Health has contributed funds towards this program.

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Continued from front cover and grooming aids or any object that may come into contact with blood or body fluids • covering all cuts and open sores with a plaster or bandage. • following standard precautions when handling blood spills If you acquire both HBV and HDV at the same time, this is called coinfection. If you are infected with HDV after already having hepatitis B, this is called superinfection. Both coinfection and superinfection of hepatitis B with hepatitis D can lead to more severe health complications than HBV infection alone. Coinfection generally resolves spontaneously after about 6 months, but it can also sometimes lead to a life-threatening or fatal liver failure. Superinfection is the more common form,

and leads to more severe liver disease than a chronic hepatitis B infection alone.

each virus particle) in order to reproduce themselves and thrive.

Up to 90% of superinfected individuals will develop chronic hepatitis D, and of these around 70% will develop cirrhosis. To compare, around 15-30% of those infected with hepatitis B alone develop cirrhosis. The two viruses in combination are the most lethal of all hepatitis infections, with a fatality rate of around 20%.

HDV coinfection is most common in China, Russia, Africa, the Middle East, parts of Eastern Europe and the Amazonian river basin in South America. It is estimated to affect around 20 million people worldwide.

Hepatitis D is the smallest known virus which can infect humans. Its tiny size means it does not contain all the organic machinery it would need to survive on its own. Hepatitis D can only survive in the bodies of those also living with hepatitis B. Hepatitis D virus particles are actually defective, and have to make use of hepatitis B’s envelope proteins (part of the “skin” that surrounds

Map courtesy Eiger Biopharmaceuticals

Global distribution of HDV and its main genotypes

There are at least 8 different strains of HDV, known as genotypes, each with a distinct way in which the disease progresses. Of the more common strains, genotypes 1 and 3 are more severe, and genotype 2 milder. Although most people living with HDV have been infected with only a single genotype, multiple exposures to the virus can lead to infections with multiple genotypes, and a more severe reaction to the virus. Because HDV requires HBV to survive, you can protect yourself by getting vaccinated for hepatitis B. In South Australia, all babies are given this vaccine as part of the National Immunisation Program. Many others can receive free hepatitis B vaccination through the High Risk Hepatitis B Immunisation Program. For more information, ring the Hepatitis SA Info Line on 1800 437 222, or talk to your GP.

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HDV Treatment

A look at what the future holds Currently there is no approved treatment for acute or chronic HDV infection. Pegylated interferon alpha is the only drug that has been shown to be somewhat effective against HDV. It acts by stimulating the body’s immune system to get rid of the virus. A small percentage—less than 30%— experience remission when injected weekly over 48 weeks. Oral nucleosides, already approved for hepatitis B treatment, have also been

used for HDV when interferon therapy is not possible and there is a high hepatitis B viral load. Unfortunately, results have shown that these have not been very effective. There are, however, a number of promising new drugs in development or being tested further, offering hope to those living with hepatitis D.

Pegylated Interferon Lambda Pegylated-interferon-lambda (PEG-IFN-λ) is a drug which

stimulates the body’s own immune responses in order to attack hepatitis D (and other viral) infections. It is intended to work similarly to the medications used for a long time to combat hepatitis C infections. Lambda has now been granted “Orphan Drug Designation” by the FDA in the United States, which means that the pharmaceutical company receives special financial concessions for working on it as a medication for a relatively rare disease.

Drugs in Development for Hepatitis D DRUG

Pegylated-interferonlambda Ezetimibe

immune response stimulator NTCP inhibitor

Myrcludex B

entry inhibitor

Lonafarnib

prenylation inhibitor surface antigen inhibitor immune response stimulator RNAi gene silencer

REP 2139, REP 2165 GI-18000 ALN-HDV

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MECHANISM

COMPANY

STATUS

Eiger BioPharma, Orphan drug USA designation

Ziauddin University Phase II trials Hospital, Pakistan MYR-GmbH, Phase II trials Germany Eiger BioPharma, Phase II trials USA Replicor, Canada Phase II trials GlobeImmune, USA

Pre-clinical trials

Alnylam, USA

Pre-clinical trials

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with interferon, in reducing hepatitis D viral levels.

Lonafarnib Ezetimibe Ezetimibe is a drug that lowers blood plasma cholesterol levels. It acts by decreasing cholesterol absorption in the small intestine. It can also be used to block the pathway by which hepatitis B and D enter hepatocytes (liver cells), and may lead to a decline in virus levels.

Myrcludex B This drug is also an “entry inhibitor” that inhibits virus entry into hepatocytes (liver cells) and has shown activity against the hepatitis B virus. It may also hinder the establishment of HDV infection in the same way, and help block reinfection as well. A recent study showed promise for Myrcludex B, when combined

This drug works by targeting the protein assembly process, which is where the virus hijacks the body’s machinery for creating new proteins and uses it to create new virus particles instead. In a recent clinical trial, Lornafib was used in combination with Ritonavir (which is usually used to treat HIV/AIDS). This combination showed promise in reducing hepatitis D viral levels, and the United States FDA has granted it fast-track status, since this class of drugs was originally developed for the treatment of cancers and has been shown to be safe.

Rep 2139 This compound is known as a “Nucleic acid-based Amphipathic Polymer” (NAP) which inhibits the release of certain hepatitis B virus particles from infected liver cells. It is being evaluated to

see how it affects hepatitis D viruses, in combination with pegylated interferon, a common hepatitis C treatment.

GI-18000 While it is in the very early stages of research, it is hoped that GI-18000 can be used to boost the body’s immune response against cells infected with hepatitis D. The current challenge is to identify different ways in which HDV-infected cells differ from uninfected cells, so that the GI-18000 will attack only the former.

ALN-HDV This pharmaceutical approach is being used against both the hepatitis B and hepatitis D viruses. The mechanism is intended to ‘silence’ the viral RNA (the collection of genetic instructions that allow the virus to reproduce), and to disrupt and destroy the viruses’ genetic structure.

This article has been expanded with permission from information provided by Hepatitis Delta Connect, a project of the Hepatitis B Foundation, based in the United States. Their website at hepdconnect.org is full of useful hepatitis D resources, and the broader foundation publishes a huge amount of hepatitis B information at hepb.org.

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Living with Hep D Afia’s Story

Two personal experiences

In 2002, I was studying in Pakistan, for my Secondary School Certificate examinations. A chain of adverse events started when I was discovered suffering from hepatitis B during a medical check up. I was told that every year about 15 to 20 students at the college were being detected with this disease—“black jaundice”, as we called it. Due to its dire consequences, I was very shocked and in despair. I rang my parents to break this bad news. They advised me to apply immediately for sick leave. Thus, I soon found myself heading back to my home in Jacobabad.

I asked him how I got the infection. His answer was that the infection was being spread in my region due to re-use of disposable syringes, the improper sterilisation of equipment, and unsterile treatment by injections and

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Image CC Amanda Mills

The very next morning, my father and I headed to Karachi to consult some medical specialists. Although the liver doctor did not prescribe any medication, he did recommend a check-up every 6-12 months. He reassured me that I was a “healthy carrier” of hepatitis B and did not require any treatment. We later learned that there is no such thing as a “healthy carrier”.

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After getting this information, and thinking that I was healthy enough, my morale improved and we returned home. But in 2011, I broke down with a fever, nausea and body aches. My eyes turned yellow. Indeed, my whole body acquired a

Radha’s Story

As a child I turned yellow with jaundice twice. I had bad abdominal pains, vomiting and fever. I spent many weeks in the hospital at ages eight and thirteen. My knees hurt as well. However, no doctor could figure out what I had. After many examinations all I was prescribed was hydrocortisone to alleviate my knee soreness. As I grew up, the stomach aches persisted and became even more frequent.

yellowish tinge. I returned back to Karachi once again, where I got an appointment with a different hepatologist. My treatment began with some medication, and I had quite a few tests. The treatment at the hands of this doctor, however, did not return me to health. The doctor told me that I was infected with hepatitis D, in addition to the hepatitis B which I already had acquired. He told me that this virus infected only those who were positive for hepatitis B, and the infection is blood-borne like hepatitis B.

to the doctor in all that time. But finally, in June 2011, as I was being prepared for a gynaecological surgery, they found that I had a hepatitis B and hepatitis D infection. I have two children and

I left that doctor in a state of hopelessness, and I opted for a 6-month homeopathic treatment, which did nothing. My liver tests did not return to normal. Finally, I approached another liver doctor who recommended a liver biopsy and a test to quantify the burden of the hepatitis D virus in my blood. On my next appointment, after reviewing my tests, he told me that the virus had significantly affected my liver. He advised me to have weekly injections of pegylated interferon. I have now started treatment for my condition.

fortunately they are healthy. So is my husband. I am currently receiving several meds and I feel quite good. I finally know what I have, and can work on fixing it.

Jaundice showing as yellow colour in the eyes Image courtesy CDC Public Health Image Library

infusions. I had never been vaccinated against hepatitis B. It was possible that I might have contracted the virus during childhood. The doctor advised me to have a separate array of household items such as soaps, razors and towels for my own use, and to screen the rest of the family for hepatitis B.

When I got older, things seemed to improve. For 15 years, I felt fine. I didn’t go

Original interviews gathered by the Hepatitis Delta International Network, and used with permission; names have been changed to protect privacy

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Hepatitis D Resources Where to go next for information Despite having been identified in the mid-1970s, hepatitis D is still a relatively little-known disease, and the information available for non-specialists is unfortunately limited. Even a global organisation like the World Hepatitis Alliance has virtually no information on hepatitis D available. So here are some of the resources you might like to investigate for further information. Mario Rizzetto (born in 1945) is an Italian virologist who was the first, in 1977, to find hepatitis D, discovering it in patients infected with HBV who had severe liver disease. He originally thought it was part of the hepatitis B virus. Although it contains a lot of technical language, Rizzetto’s short history of research into the virus and its treatment, available in full at bit. ly/2AIKvnh, is a useful and comprehensive summary.

For more general information, Hepatitis Australia’s hepatitis D page at bit.ly/2yNqN87 is a brief beginner’s guide to the virus. SA Health offers similar information at bit. ly/2AJ8VNB, as well as details of the virus’s status as a notifiable condition in this state. Further health information can be found

under the links for hepatitis B at both these sites. Finally, the resources provided online at hepdconnect.org by the Hepatitis B Foundation (see p4–5) are the most comprehensive available, and news updates appear regularly at twitter.com/ hepdconnect.

hepsa.asn.au

Virology educator Professor Cihan Yurdaydin has written a useful (but also quite technical) roundup of recent advances in managing hepatitis D for the US National Library of Medicine. You can download it in full at bit.ly/2j8NCh2. He has also co-authored a guide to therapy research at bit. ly/2CNo5Tj. A collection of other fully accessible HDV technical and research papers can be found at bit.ly/2BxYCj9.

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